Conclusions
C3 contributes to fibrinolysis, as inhibition with Compstatin enhanced fibrinolysis, and CVF cleavage of C3 decreased fibrinolysis. CVF also induced a hypercoagulable state with increased clot strength.
Methods
C3/C5 convertase Cobra Venom Factor (CVF, 10 Units/mL) was employed to activate the alternative complement pathway in whole blood. Complement inhibition was completed with inhibitors for C3/C3b (Compstatin, 25 and 50 μM), C3a receptor (SB290157, 300 nM, C3aR), and C5a receptor (W54011, 6 nM, C5aR). Coagulation was assessed using native thrombelastography which produces the following: reaction time (R time); angle; maximum amplitude (MA); percent fibrinolysis at 30-min post-MA (LY30).
Results
Inhibition with C3aR and C5aR inhibitors did not alter clot formation (R time, 11.2 vs 11.6 min, P = 0.36), clot strength (MA, 52.0 vs 52.3 mm, P = 0.43), or fibrinolysis (LY30, 1.6 vs 4.0%, P = 0.19). Compstatin did not influence clot formation or clot strength but did induce a dose-dependent increase in fibrinolysis (control LY30 3.0 vs 7.8% and 12.4% for 25 and 50 μM respectively, P = 0.0002). CVF increased MA (58.0 vs 62.8 mm, P < 0.0001), decreased LY30 (2.3 vs 1.4%, P = 0.004), and increased R time (8.4 vs 9.9 min, P = 0.008). Compstatin reversed the effects of CVF, while C5a reversed only the change in LY30. Conclusions: C3 contributes to fibrinolysis, as inhibition with Compstatin enhanced fibrinolysis, and CVF cleavage of C3 decreased fibrinolysis. CVF also induced a hypercoagulable state with increased clot strength.